Reed-Sternberg cells of Hodgkin's disease express CD30 and CD40 receptors. The ligands for these receptors have been reported to have pleiotropic biologic activities in vitro, including induction of cell death and enhancing cell survival. Co-expression of the ligands for these receptors in lymph nodes involved with Hodgkin's disease is not known.The purpose of this study was to examine CD30 ligand (L) and CD40L expression in lymph nodes of patients with Hodgkin's disease, and to study CD30L expression on nodal lymphocyte subsets.CD30L expression on subsets of lymphocytes of five lymph nodes involved with Hodgkin's disease was determined by two-color FACScan. Messenger RNA expression of CD30L and CD40L was determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) method performed on seven specimens involved with Hodgkin's disease (five lymph nodes and two spleens).Four of seven specimens (57%) contained cells that expressed CD30L mRNA and three specimens (43%) contained CD40L-expressing cells. The mean percentage of nodal lymphocytes expressing CD30L surface protein was < or = 20%.Hodgkin's disease lymph nodes and spleens frequently lack CD30L- and CD40L-expressing cells, and when CD30L is expressed, it is usually detected on few numbers of lymphocytes. The balance in the level of expression of these ligands in Hodgkin's disease lymph nodes may be related to the disease's clinical behavior.